ABSTRACTObjectiveThe US Food and Drug Administration established the De Novo premarket review pathway for first-of-a-kind moderate-risk devices in 1997 in order to reduce barriers to technological innovation and patient access. We sought to characterize three key features of this pathway: (1) the strength of clinical evidence supporting FDA clearance of therapeutic De Novo devices; (2) FDA post-marketing requirements for these devices; and (3) use of these devices as the basis for devices subsequently cleared via the 510(k) process.DesignRetrospective cross-sectional analysisSettingPublicly available online FDA databases, including the De Novo database, the 510(k) clearance database, the 522 Post Market Surveillance database, and the Recalls of Medical Devices databaseParticipantsAll moderate-risk therapeutic devices cleared via the De Novo pathway between January 1, 2011, and December 31, 2019.Main Outcome Measures(1) proportion of De Novo devices cleared based on evidence from a pivotal clinical study, (2) proportion of pivotal study primary effectiveness endpoints that were met, (3) proportion of De Novo devices subject to FDA-required postmarket studies, and (4) proportion of De Novo devices serving as the basis for at least one subsequently cleared 510(k) device (i.e., new models or competitor products).ResultsThere were 63 (of 65; 96.9%) moderate-risk therapeutic devices cleared by FDA via the De Novo pathway between 2011 and 2019 for which decision summary documentation was publicly available. Of the 63 devices, 51 (81.0%) were supported by pivotal clinical studies (n=54 studies); the remainder (n=12; 19.0%) were not supported by a pivotal clinical study. The majority of pivotal studies were randomized (57.4%), multi-armed (61.1%), and used an active (25.9%) or sham (35.2%) comparator arm; 17 (31.5%) failed to meet at least one primary effectiveness endpoint. Among the 63 devices cleared via the De Novo pathway, one (1.6%) was subject to an FDA-required posttmarket study and 32 (47.8%) served as a predicate device for new models or competitor devices subsequently cleared through the 510(k) process.ConclusionsBetween 2011 and 2019, the FDA cleared the majority of first-of-a-kind moderate-risk therapeutic devices via the De Novo pathway based on premarket evidence from pivotal clinical studies. However, 43% of devices were cleared without clinical evidence from pivotal studies or based on pivotal studies that failed primary effectiveness endpoints. The FDA rarely required postmarket studies of these devices, which often served as the basis for new models and competitor products subsequently cleared via the 510(k) process.KEY POINTSWhat is already known on this topicThe US Food and Drug Administration (FDA) established the De Novo premarket review pathway for first-of-a-kind moderate-risk devices in 1997 in order to reduce barriers to technological innovation and patient access.In recent years, manufacturers have increasingly received FDA clearance to market devices through the De Novo pathway.The importance of the De Novo pathway will continue to grow as the FDA seeks to expedite patient access relative to international regulators.What this study addsAlthough the FDA clears the majority of therapeutic De Novo devices based on premarket evidence from pivotal clinical studies, 43% were cleared without such evidence or based on pivotal studies with failed primary effectiveness endpoints.The FDA rarely required postmarket studies of therapeutic De Novo devices, which often served as the basis for new models and competitor products subsequently cleared via the 510(k) process.
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